Demonstration of human papillomavirus (HPV) type 30 in
esophageal
squamous-cell carcinomas by in
situ
hybridization (letter). F Chang, S Syrjänen, K Syrjänen. Int
J Cancer 1993;55:171-173. HPV-30 was present in 8 (9.4%) of 85
HPV-positive esophageal carcinomas. "5 were infected with the HPV-30 as
the single type, and 3 patients were co-infected with other HPV types,
1 with HPV 6/11 and 2 with HPV 16... The original isolation of HPV 30
from a laryngeal squamous-cell carcinoma indicates that this virus can
exert an oncogenic potential on epithelial cells. The identification of
HPV 30 DNA in 2.2% (8/363) of esophageal squamous-cell carcinomas
points to a causal role for this HPV type in the pathogenesis of
esophageal carcinoma."

Human papillomavirus (HPV) infections in carcinogenesis of the
upper
aerodigestive tract. K Syrjanen & Kuopio Papillomavirus
Research
Group (S Syrjanen, R Mantyjarva, S Saarikoski, F Chang, S Parkkinen, M
Yliskoski, T Nurmi, V Kataja, J Kellokoski, M Hippelainen, A
Tervahauta, J Janne, L Albonen). Research proposal to the Council for
Tobacco Research, estimated date 1993. "HPV infection in human
esophagus was first suggested in 1982 by Syrjanen et al., who found
that 40% (24/60) of esophageal squamous cell carcinomas presented with
histological changes identical to those of genital (HPV-induced)
condylomas... These results have been confirmed by others
demonstrating HPV-suggestive lesions, HPV antigens as well as HPV DNA
sequences in esophageal squamous cell lesions." The Kuopio
Papillomavirus Research Group's work was virtually the only
research on
infection as the fundamental cause of chronic disease that the CTR
funded - and then they never used the data. Start page 12.

Detection of human papillomavirus in esophageal squamous cell
carcinoma. L Suzuk, AE Noffsinger, YZ Hui, CM Fenoglio-Preiser. Cancer
1996 Aug 15;78(4):704-710. Out of 110 tumors, they did not find any HPV
in any specimen by ISH or by PCR.

Human papillomavirus type 16 is an important infectious factor
in
the high incidence of esophageal cancer in Anyang area of China. T Li,
Z-M Lu, K-N Chen, M Guo, H-P Xing, Q Mei, H-H Yang, JF Lechner, Y Ke.
Carcinogenesis 2001 Jun;22(6):929-934. "Esophageal carcinoma is one of
the major cancers in China. The area of Anyang is located at the foot
of Tai Hang Mountain in Henan province and has the highest incidence
and mortality of esophageal cancer in China. Extensive investigations
on natural geographic environment, life habits and trace elements in
the diet have failed to establish the etiology of esophageal cancer in
this district." In volunteers, 72% in the high incident village and 37%
in the low incident village were infected, mainly by HPV-16.

HPV infections and esophageal cancer. KJ Syrjanen. J Clin
Pathol
2002;55(10):721-728. Review. "To date, 239 oesophageal squamous cell
papillomas have been analysed in 29 separate studies using different
HPV detection methods, with HPV being detected in 51 (21.3%) cases.
Many more squamous cell carcinomas have been analysed: of the 1485
squamous cell carcinomas analysed by in situ hybridisation, 22.9% were
positive for HPV DNA, as were 15.2% of the 2020 cases tested by the
polymerase chain reaction."

Detection of human papillomavirus in esophageal carcinoma. ZY
Shen,
SP Hu, LC Lu, CZ Tang, ZS Kuang, SP Zhong, Y Zeng. J Med Virol 2002
Nov;68(3):412-416. In 176 esophageal cancer patients, for HPV type 6,
11, 16, and 18, "The incidence rate was 65.5%, 69.1%, and 60% in
tissues of cancerous, paracancerous and normal mucosa, respectively.
Further analysis of the distribution of HPV types in the three sections
of tissues showed that the high-risk HPV types 16 and 18 were found
mainly in the cancer cells (43.2%), whereas the low-risk HPV types 6
and 11 were seen mainly in the normal mucosa (52.3%). The total
infection rate of the high-risk HPV types 16 and HPV 18 was the highest
in cancerous tissues (54.5%), followed by paracancerous tissues
(19.5%), and the lowest in normal mucosa (11.7%).

Viral load of HPV in esophageal squamous cell carcinoma. HX
Si, SW
Tsao, CS Poon, LD Wang, YC Wong, AL Cheung. Int J Cancer 2003 Feb
10;103(4):496-500. "HPV infection was detected in 2-22.2% of samples.
Infection with HPV-16 was again shown to be more common than that with
HPV-18 among Chinese ESCC patients. The copy number of HPV-16 in these
ESCC cases ranged from < or =1 to 157 copies/genome equivalent,
with
65% of samples harboring fewer than 10 copies/genome equivalent. The
median copy number of HPV-18 was 4.9/genome equivalent."

[Expression of HPV16-E6 and E7 oncoproteins in squamous cell
carcinoma tissues of esophageal cancer and non-cancer tissues]. CL Xu,
XL Qian, XS Zhou, QZ Zhao, YC Li. Ai Zheng 2004 Feb;23(2):165-168.
"HPV16-E6
and E7 oncoproteins were determined using immunohistochemical staining
in normal mucosa tissues (70 cases), dysplasia tissues (43 cases), and
carcinoma tissues (18 cases). RESULTS: The positive rates of HPV16-E6
in the tissues of normal mucosa, dysplasia, and carcinoma of esophagus
patients were 59.3%, 88.4%, and 83.3%, respectively; the positive rates
of
HPV16-E7 protein were 62.1%, 90.7%, and 88.9%, respectively. The
positive rates of HPV16-E6 and E7 in dysplasia and carcinoma of
esophagus were significantly higher than those in normal mucosa
(P<
0.05). Double expression of HPV16-E6 and E7 in normal mucosa was 25.7%,
while in dysplasia and carcinoma were 88.3% and 83.3%, respectively.
CONCLUSION: HPV16-E6 and E7 are highly associated with esophageal
squamous cell carcinogenesis. And cooperation of HPV16-E6 and E7 may
play an important role in genesis of esophageal squamous carcinoma."

Esophageal squamous cell cancer in patients with head and neck
cancer: Prevalence of human papillomavirus DNA sequences. EM de
Villiers, K Gunst, H Stein, H Scherubl. Int J Cancer 2004 Mar
20;109(2):253-258. Fresh-frozen random esophageal biopsies from 60
patients screened for asymptomatic ESCC, and 21 paraffin-embedded
specimens with pairs of HNC and ESCC. "HPV DNA sequences were detected
in 66.7% of normal/inflammatory (34/51) and dysplastic and malignant
(6/9) esophageal tissues from HNC patients being screened
endoscopically. Similarly, in the second group of 21 patients with both
HNC and ESCC, HPV DNA sequences were demonstrated in 13 (61.9%) of the
HNC biopsies and in 14 (66.7%) of the ESCC biopsies. The prevalence of
high-risk-type HPV 16 was low (5/51, 9.8%) in normal/inflammatory
esophageal mucosa but higher (10/24, 47.6%) in ESCC. The low-risk HPV
11 was present in 37.3% (19/51) of normal/inflammatory, 66.7% (4/6) of
dysplastic and 28.9% (13/45) of the carcinoma samples."

p53 gene mutation and human papillomavirus (HPV) infection in
esophageal carcinoma from three different endemic geographic regions of
India. S Katiyar, S Hedau, N Jain, P Kar, MS Khuroo, J Mohanta, S
Kumar, V Gopalkrishna, N Kumar, BC Das. Cancer Lett 2005 Jan
31;218(1):69-79. "Out of a total of 101 biopsy specimens of carcinoma
esophagus analysed, the frequency of HPV was found to be the highest
14/32 (44%) in Dibrugarh followed by 33% (11/33) in Kashmir, but,
interestingly, no high-risk HPV could be detected in New Delhi patients
who showed the highest frequency (30.6%) of p53 mutation as against
only 12.5% in Dibrugarh and 6.1% in Kashmir."

Identification of human papillomavirus in esophageal squamous
papillomas. OL Bohn, L Navarro, J Saldivar, S Sanchez-Sosa. World J
Gastroenterol 2008 Dec 14;14(46):7107-7111. "HPV was detected in 14 of
16 cases (87.5%) by ACISH: Twelve showing a diffuse and complete
nuclear staining pattern (indicating the episomal state of the HPV
viral genome, Figure 1A) and two a nuclear granular pattern (indicating
the integrated form of the HPV viral genome, Figure 1B). HPV DNA was
identified by PCR in 12 of 14 cases (85.7%). Infection by a low risk
type HPV (6/11) was detected in 10 of 14 cases, whereas two of the 14
cases were infected by a high risk HPV type (16). Both high risk cases
showed a granular staining pattern on ACISH, suggesting viral genomic
infection. In two cases, ACISH demonstrated a diffuse pattern and HPV
was not documented by PCR."

Human papilloma virus and esophageal carcinoma in a
Latin-American
region. R Herrera-Goepfert, M Lizano, S Akiba, A
Carrillo-García, M Becker-D'Acosta. World J Gastroenterol 2009
Jul 7;15(25):3142-3147. "HPV was detected in 15 (25%) of ESCCs. HPV-16
was the most frequently observed genotype, followed by HPV-18; HPV-59
was also detected in one case... HPV presence in ESCC was not
significantly associated with gender, age, alcohol consumption,
smoking, anatomic location, or histologic grade. All patients belonged
to low and very low socioeconomic strata, and were diagnosed at
advanced disease stage." Males were most often affected.

Detection of HPV DNA in esophageal cancer specimens from
different
regions and ethnic groups: a descriptive study. X Wang, X Tian, F Liu,
Y Zhao, M Sun, D Chen, C Lu, Z Wang, X Shi, Q Zhang, D Zhang, Z Shen, F
Li, CC Harris, H Cai, Y Ke. BMC Cancer 2010 Jan 16;10:19. 244 of 435
samples (56.1%) tested positive for HPV L1. "Significant differences in
detection rate were observed neither among the three areas of China nor
between China and the US. HPV6, 16, 18, 26, 45, 56, 57, and 58 were
identified in L1 positive samples. HPV16 and 57 were the most common
types in all regions, followed by HPV26 and HPV18. CONCLUSIONS: HPV
infection is common in esophageal carcinoma independent of region and
ethnic group of origin. Findings in this study raise the possibility
that HPV is involved in esophageal carcinogenesis. Further
investigation with a larger sample size over broader geographic areas
may be warranted." Detection rates were similar in adenocarcinomas and
squamous cell carcinomas. HPV load is lower in esophageal than in
cervical cancer, which results in false negatives in other studies.

Infection and integration of human papillomavirus in
esophageal
carcinoma. QY Zhang, DH Zhang, ZY Shen, LY Xu, EM Li, WW Au. Int J Hyg
Environ Health 2011 Mar;214(2):156-161. 106 esophageal tumor
tissues and paired adjacent normal tissues, 100 normal controls. "The
detection rates of HPV DNA in EC and tumor-adjacent tissue were
significantly higher than that in normal controls (77.4% and 80.2% vs.
33.0%). HPV infection was mainly found in adults, ages 35-47 years old,
and the infection rate was negatively associated with the age of EC
patients (P-trend<0.05). In addition, the HPV infection rates in
patients who smoked was 3.27 times higher than in non-smoking patients
(84.9% vs. 67.4%, P<0.05) but was not associated with gender,
alcohol consumption, tumor grade or lymph-node metastasis of EC
patients. The distribution of HPV genotypes in patients from high to
low proportion was HPV-16, -58, -18, -33, -31 and -11. Infection with
multiple HPV genotypes mainly included HPV-16/-18 and HPV-16/-33. The
integration rate of HPV-16 in EC tissue was higher than that in
tumor-adjacent and control tissues (93.4% vs. 50.9% and 45.5%)."

Geographic origin is a significant determinant of human
papillomavirus prevalence in oesophageal squamous cell carcinoma:
Systematic review and meta-analysis. K Syrjänen. Scand J Infect Dis
2013 Jan;45(1):1-18. "These 152 studies covered a total of 10,234 ESCC
cases, analysed by different HPV detection methods in different
geographic regions. Of these 10,234 cases, 3135 (30.6%) tested
HPV-positive, translating to an effect size of 0.372 (95% CI
0.360-0.384; fixed effects model) and 0.290 (95% CI 0.251-0.31; random
effects model)... Conclusions: These meta-analysis results indicate
that the reported wide variability in HPV detection rates in ESCC is
not due to the HPV detection techniques, but is explained by the
geographic origin of the study. These data substantiate the recently
elaborated concept that ESCC might have a different aetiology in
low-incidence and high-incidence geographic regions, HPV playing an
important role only in the latter."

High
prevalence of human papillomavirus in esophageal squamous cell
carcinoma: a study in paired samples. K Vaiphei, R Kochhar, S
Bhardawaj, U Dutta, K Singh. Dis Esophagus 2013 Apr;26(3):282-287. HPV
was positive in 20/23 (87%) patients. Most had more than one viral
type. "HPV52 was the most common observed in 14 (61%) males and two
(9%) females. Other common viruses were HPV55, 39, and 59. Smoking had
a significant association with viral positivity. p63 and p16
oncoproteins correlated with degree of tumor differentiation but not
with viral status."

Evidence
for the aetiology of human papillomavirus in oesophageal squamous cell
carcinoma in the Chinese population: a meta-analysis. SS Liyanage, B
Rahman, Z Gao, Y Zheng, I Ridda, A Moa, AT Newall, H Seale, Q Li, JF
Liu, CR Macintyre. BMJ Open 2013 Nov 15;3(11):e003604. "Of a total of
1177 OSCC and 1648 oesophageal control samples, 55% (642/1177) of
cancer specimens and 27% (445/1648) of control samples were positive
for HPV DNA. A positive strong association between HPV DNA and OSCC was
observed among the included studies, with a pooled OR of 3.69 (95% CI
2.74 to 4.96). Heterogeneity and publication bias were not observed in
the analysis. Subgroup analyses of the included studies also supported
the measure of association of causal links between HPV and OSCC."

The
absence of human papillomavirus in esophageal squamous cell carcinoma
in East China. H Teng, X Li, X Liu, J Wu, J Zhang. Int J Clin Exp
Pathol 2014 Jun 15;7(7):4184-4193. 177 tumor samples. "The genotyping
results showed that only six samples were weakly positive for HPV: two
for HPV16, two for HPV11 and two for HPV35, with no samples showing
strong positive signals. The IHC results showed only five samples with
diffuse positive staining, with the other samples being completely
negative or having only focal positive signals, which were considered
as negative."